This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Delaware INBRE P20 RR016472-09 Year 9 Annual Progress Report Shared Research Instrumentation Core Core Directors: Kirk Czymmek, UD [unreadable]Chair; Katia Sol-Church, Nemours The core instrumentation centers, partially supported by INBRE-2 funding, play a key role in facilitating life-sciences-based research across the State of Delaware. Although many of the core centers are located at the Delaware Biotechnology Institute (DBI) and departments within the University of Delaware (UD) special emphasis has now been placed to expand participation of cores from within UD as well as our partner institutions. This participation, initially focused on cores that support our INBRE faculty and life sciences research, encourages exchange beyond those directly supported by INBRE funds. An example of the cross-institutional involvement is regular attendance and feedback from as many as 11 core facilities including DBI Bioinformatics, Nemours Cell Science, UD Center for Translational Cancer Research, Christiana Care Center for Translational Research, DBI Proteomics, UD Sequencing/Genotyping, Nemours Histology, Nemours Biomolecular Core, Christiana Care Center for Outcomes Research, DBI Protein Production, DSU Bio-Imaging, DBI Bio-Imaging, UD Keck Imaging Center and DBI Administration. The core center directors meet on a bi-monthly basis to discuss strategies for broadening the interest and user base among Delaware's research community. The primary over-arching goal of this core will be to support INBRE Investigators through improved networking, communication, visibility and functioning of core facilities. Under the leadership of Director, Dr. Kirk Czymmek (DBI Bio-Imaging) and Co-Director Dr. Katia Sol-Church (Nemours Biomolecular Core) the meetings are centered on achieving this goal via the following objectives: 1. Expand the Core Network by increasing the number of cores participating. 2. Build technical resources. 3. Enhance facility operation through efficiency gains and improved project/work flow. Early meetings in summer of 2009 led to the creation of a Core Director Users Group (under the alias, CoreDirectors@dbi.udel.edu) supported by DBI Bioinformatics. This users group allows rapid exchange and dissemination of information of core related resources, education and meetings and scientific exchange. Although only a handful of meetings have been held since the INBRE renewal, the Core Facilities Core is well on its way toward enhancing the core infrastructure for its targeted investigators. One major initiative includes working to create a searchable centralized web-based resource for shared and core equipment. Equipment listings for core centers currently can be accessed through a dedicated web portal under www.dbi.udel.edu/coreinstrumentation.html. At this site, information is provided with web-based instrument descriptions, on-line reservation calendars, billing and assessment tools to optimize access and use of these resources. However, core facility directors believe that expansion of capabilities (including a searchable database and core websites with their sub-directories) and centralization of numerous similar campus-wide and partner institution equipment lists will be highly valuable. Some regional core instrumentation searchable databases exist (i.e., Harvard Catalyst, Vermont Genetics Network) and may serve as models, but do not necessarily have all the features that would support our needs. In an effort to avoid duplication with other similar efforts on campus, early conversations are being held with Dr. Karl Steiner and Dr. Douglas O'Neal to create such a centralized core facility and equipment resource. A second major initiative in the last few months is the creation of a centralized web-based equipment scheduling calendar, project tracking and data sharing resource. Although suitable core facility management software with all these functions may not exist, we have begun exploring the possibility of customizing commercial software that could be used by numerous core facilities and shared equipment campus and state-wide. ElabExperts, Inc. (www.ElabExperts.com) has been identified as one possibility in our December 2009 meeting during a presentation of functionality. Beta-testing software will be possible in the Bio-Imaging Center and other cores in January 2010 and if it meets our needs, plans are underway to seek funds to make a centralized version available to interested cores. As in previous years, special consideration is placed on securing equal access for faculty and students at any of the partner institutions in the statewide INBRE Network. All of Delaware's researchers are less than two-hour travel distance from the core centers, and high-speed Internet connectivity enables remote desktop access to the bioinformatics center and to the Bio-Imaging facilities, where internet-based access to microscopy resources is possible. The INBRE program continues to provide support the Core Instrumentation Centers through the following four mechanisms: 1) Instrumentation upgrades to support the research goals of the INBRE investigators;2) Partial salary support for Core Center staff to ensure the professional operation of the instruments;3) Instrumentation maintenance in the amount of $15,000;and 4) Core Center Fee Waivers in the amount of $40,000 for faculty and students in the INBRE partnership to allow them to use the core centers to obtain initial data and provide startup-support for new scientific ideas. Investments: In 2008-2009, the Core Centers have received instrumentation major upgrades/purchases that were funded by a variety of sources. This continues to indicate that the initial INBRE investments into the Core Centers are beginning to translate into success with attracting other funding sources, paving the way toward long-term sustainable core centers. The most significant installations are listed below: 1) Zeiss LIBRA 120 PLUS Transmission Electron Microscope ($520,000) After a thorough evaluation of the leading manufacturers of 120 kV Transmission Electron Microscopes with Tomography capabilities, we selected the Zeiss LIBRA 120 PLUS Transmission Electron Microscope. As requested, the system has a least +/-70[unreadable] specimen tilt for 3D tomography applications and can be equipped with either a LAB6 or tungsten filament. The selected system also has energy filter functionality, which will allow high-resolution identification and mapping of nanoparticles and elements that are relevant to human health. In addition, the energy filter enables extremely high-contrast imaging of unstained biological and biomaterial samples. The chosen system has a full complement of automated digital acquisition, alignment, reconstruction, processing, measurement and analysis tools. The microscope is cryo-capable for low dose imaging when we are ready to upgrade to this enhancement in the near future. The Zeiss LIBRA 120 PLUS was installed in the Delaware Biotechnology Institute Bio-Imaging Center during the week of March 13-17th, 2009. The system is now fully operational and numerous INBRE projects are utilizing the new capabilities. The Bio-Imaging Center is an outstanding state-of-the-art microscopy facility which support all forms of biological and biomedical microscopy for the University and local hospitals (i.e., Christiana Care Hospital, Nemours A.I. DuPont Hospital for Children) and industry (Fraunhofer, W.L. Gore, Astra Zeneca) to name a few. Funds for this microscope came from the U.S. Department of Health and Human Services, Health Resources and Services Administration grant with Dr. Karl Steiner as PI ($359,901) with the balance ($160,099) coming from DBI, INBRE and DBI Bio-Imaging Center. 2) Illumina Sequencing-by-Synthesis (SBS) Machine ($625,000) This "next-generation" high-throughput sequencing instrument now serves as a cornerstone of a significantly expanded DNA sequencing facility to support the research and development of novel applications. This system was funded and installed in 2008 and finally fully operational earlier this year and in a very short time has generated over 101 Gbp of data. This advanced sequencing technology frees the user of traditional cloning techniques, in the process eliminating most of the bias, cost, and labor associated with traditional DNA sequencing. The SBS instrument provides a large number of short reads (35 to 50 nucleotides) and generates a significant amount of data per instrument run. This makes the technology ideal for rapidly and economically developing datasets that can be compared against an existing genomic database or where the potential for chimeric sequence assembly is low. Partial funding for this instrument was provided by the EPSCoR RII program ($250k) with significant matching contributions ($375k) from the Unidel Foundation. Plans are underway to upgrade the Illumina GAII to the GAIIx to allow longer reads capable of de novo sequencing. 3) In addition, a small but important enhancement has also been added to Nemours Biomolecular Core in the form of upgraded fluidics on Affymetrix microarray New Core Facility Related Pending and Funded Grants: In 2009, the Core Centers continued to leverage the INBRE investment into major facility research and equipment grants: For example, the DBI Bioinformatics and DNA Sequencing &Genotyping Center were part of NIH NCRR Translational Research Grant ($987,810). These UD facilities are part of a consortium that was funded with a NIH NCRR Translational Research grant ($987,810). The project goal is to perform de novo sequencing of the skate (originally dogfish shark), and develop a regional IT infrastructure. Numerous other Core Infrastructure and Equipment Grants were submitted and/or pending with key participation and leadership of core facilities: DBI Bio-Imaging + NIH GO: Bio-COSM ($4.7million). Creation of a National Resource Center for "Biological Correlative and Super-Resolution Microscopy" with requested addition of LSM 710 confocal, SIM and F-PALM super-resolution microscopes, Dual-Beam FIB scanning electron microscope and Catalyst AFM. (NIH Priority Score 35, Pending) + NIH SIG: LSM 710 Confocal ($495,000), (NIH Priority Score 29, Pending) + NIH SIG: TIRF Microscope ($385,000), (Not Reviewed) DBI + NIH G20: Renovation and Centralization of Life Science Core Facilities at UD ($10million) (NIH Priority Score 40, Pending - unlikely to be funded) + NIH RA Supplement- Business Skills Course ($750,000) (Not funded). Core Meeting Participation and Networking: The DE-INBRE Centralized Research Instrumentation Core provides leadership to both national and regional core networks through the activities of many of its members. This year INBRE provided support for interested INBRE core facility meeting participants to attend local and regional meetings. Delaware continues to have a strong representation and with INBRE support we plan to continue encouraging facility managers/directors to network in this way. Below are a few highlights over the last year: + At the regional level, the Centralized Research Instrumentation Core has promoted participation to the Northeast Regional IDeA meeting that was hosted by the Dartmouth Medical School and to the Northeast Life Science Core Directors. NERLSCD is one of the very few meetings that focus entirely on the operational issues that pertain to running shared resource facilities. Including the effective management of core resources and on the optimal application of existing and emerging biotechnologies. Thus the meeting plays a crucial role in facilitating advances in knowledge and understanding in a wide variety of NIH funded life sciences research areas. This year the NERLSCD meeting was held in November at Cornell University and members from 7 of the Delaware Core Centers were represented for this meeting (2 bioinformatics, 2 genotyping, 2 proteomics, 1 bio-imaging). Dr. Barbara Alving Director of the NCRR delivered the keynote address, and participated with Louise Ramm, Deputy Director of NCRR/NIH, and Gregory Farber, Health Scientist Administrator of the Division of Biomedical Technology of NCRR/NIH in an active panel discussion moderated by Dr. Sol-Church. + At the national level Kingham, Lee and Sol-Church are active members of the Association of Biomolecular Resource Facility (ABRF), a professional association of core lab providing benchmarking and educational opportunity to its members. These Directors have participated in research studies insuring their level of expertise remains at the leading edge, and/or organizing scientific sessions and given presentations during the society annual meetings. Of note Dr. Kelvin Lee was a panelist on the much anticipated session on "Core Facility Management Models: Development and Culture" during the ABRF2009 meeting in Memphis TN. Mr. Kingham is currently the Chair of the ABRF's Genomic Variation Research Group and Dr. Sol-Church is Chair-elect of the Association's Education Committee. + Drs. Lee and Sol-Church were invited speakers during the NCRR- Efficient Management and Utilization of Core Facilities. July 14-15, 2009 Bethesda, MD. The purpose of this conference was to discuss the state of existing NIH-funded research core facilities, identify common problems encountered during their operation and use, and raise options to maximize the use and efficiency of core facilities. Lee's talk focused on A-21 compliance and management of the core facility from the perspective of a core customer, faculty mentor, administrator and proteomics core facilitator, while Sol-Church described a proposal for a "Business Skill course for Core Center Directors" which was being developed by the DE-INBRE team Dr. Kirk Czymmek, DBI Associate Director Jeanette Miller and Dr. Katia Sol-Church. The business course proposal was submitted with Dr. David Weir as PI, but was not funded. Other mechanisms of support were being considered and pursued. + The Delaware INBRE is a strong supporter of a new initiative spearheaded by Dr. Sol-Church to build a national Network of IDeA-funded Core Laboratories (NICL) to promote the flow of technical expertise within regional and national networks of biomedical research excellence, and improve communication /cooperation between IDeA-funded core facilities. This Network will be a central resource available for INBRE/COBRE cores that will focus on technology development, core sustainability projects and enhancement of research capabilities through education and resource sharing. The Network will also provide and maintain direct cross-talk with the National Association of IDeA-funded PIs (NAIPI), and other regional and national association of core labs such as the NorthEast Regional Life Science Core Director (NERLSCD) and the Association of Biomolecular Resource Facilities. The first meeting of the NICL was held satellite to the ABRF2009 meeting. Core Facility Usage: For additional new cores (DBI Proteomics, Nemours Biomolecular Core, Nemours Cell Science Core and Christiana Care Center for Outcomes Research) now augment 3 previously INBRE supported cores (DBI Bio-Imaging, DBI Bioinformatics and DNA Sequencing &Genotyping Center). This year will serve as a baseline for the 4 new cores. The three previously INBRE supported cores, continued to demonstrate significant and strong usage over the last year. These usage statistics will be monitored over the next several years to ascertain the impact for INBRE and INBRE investigators. One of the key features of the INBRE program is the opportunity for Delaware researchers to request Core Center Fee Waivers. Faculty are invited to submit a short proposal to the RII leadership outlining the core services required, the time period, the estimated cost, and the path forward to secure external funding. In the current Year 9 of the INBRE, 12 Core Fee Waiver proposals have been selected to date for a total value of $51,750, for work in 4 core centers: bioimaging, proteomics, sequencing and protein production, to be covered by the INBRE grant. This compares to 12 proposals funded for a total value of $30,000 in Year 8. These small grants enable faculty and students across the Network to try out new ideas free of charge and to generate preliminary data to support future research proposals. Under a new process, two-page grants are submitted to the INBRE Research Committee on a monthly basis (previously quarterly) and recommended for funding if merited. Of the seven core centers funded by INBRE, four have or will be used in 2009 (Center for Outcomes Research, DBI Bio-Imaging, DNA Sequencing and Genotyping, Cell Science). Several non-funded core centers were also identified for use - Mass Spectroscopy, Center for Translational Cancer Research (CTCR), Keck Imaging Center, DSU Bioimaging, CTCR flow cytometry and mechanical engineering. Two or more investigators identified the Center for Outcome Research, DBI Bio-Imaging Center, Center for Translational Cancer Research, and the Keck Imaging center for use in 2009.